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Food Science and Human Wellness 2020年第2期9卷 136-145页

作者： Jie Lina Jinlong Tian Chi Shu Zhen Cheng yunen liu Weisheng Wang Ruihai liu Bin Li Yuehua Wang National R&D Professional Center For Berry Processing Shenyang Agricultural UniversityLiaoningPR China Key Laborotary of Healthy Food Nutrition and Innovative Manufacturing LiaoningPR China Emergency Medicine Department of General Hospital of Shenyang Military Command Laboratory of Rescue Center of Severe Trauma PLALiaoningPR China Shenyang Blueberry Industry co.LTD. LiaoningPR China Department of Food Science Cornell UniversityIthacaNYUSA

Malvidin-3-galactoside(Mv-3-gal)is the major anthocyanin monomer in blueberry anthocyanins.The compound is well-characterized by its anti-oncogenesis function in multiple organs including liver.In the current study,the mechanism driving the anti-hepatocellular carcinoma(HCC)function of Mv-3-gal was further explored by focusing on apoptosis and metastases pathways.HCC cell line Huh-7 was firstly administrated with Mv-3-gal of different concentrations and the effect of Mv-3-gal on cell proliferation,apoptosis,colony formation ability,metastasis potential as well as the activity of Akt/PTEN and MAPK pathways was assessed.The results showed that Mv-3-gal inhibited the cell proliferation and colony formation ability,induced cell cycle arrest and apoptosis in a dose-dependent manner.Regarding the metastasis potential,Mv-3-gal suppressed the migration and invasion potential of Huh-7 cells by regulating MMPs expression.Taken together,the findings highlighted the anti-HCC potent of Mv-3-gal,which was associated with the inhibition of Akt/PTEN,MAPK and MMP pathways.

关键词： Malvidin-3-galactoside Hepatocellular carcinoma Apoptosis MAPK signaling

Biomimetic inorganic-organic hybrid nanoparticles from magnesium-substituted amorphous calcium phosphate clusters and polyacrylic acid molecules

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Bioactive Materials 2021年第8期6卷 2303-2314页

作者： Na Li Wei Cui Peifang Cong Jie Tang Yong Guan Caihao Huang yunen liu Chengzhong Yu Rui Yang Xing Zhang Institute of Metal Research Chinese Academy of SciencesShenyangLiaoning110016China School of Materials Science and Engineering University of Science and Technology of ChinaHefeiAnhui230026China Department of Emergency Medicine General Hospital of Northern Theater CommandShenyangLiaoning110016China National Synchrotron Radiation Laboratory University of Science and Technology of ChinaHefeiAnhui230029China Australian Institute for Bioengineering and Nanotechnology The University of QueenslandBrisbaneQLD4072Australia

Amorphous calcium phosphate(ACP)has been widely found during bone and tooth biomineralization,but the meta-stability and labile nature limit further biomedical applications.The present study found that the chelation of polyacrylic acid(PAA)molecules with Ca^(2+)ions in Mg-ACP clusters(~2.1±0.5 nm)using a biomineralization strategy produced inorganic-organic Mg-ACP/PAA hybrid nanoparticles with better thermal stability.Mg-ACP/PAA hybrid nanoparticles(~24.0±4.8 nm)were pH-responsive and could be efficiently digested under weak acidic conditions(pH 5.0-5.5).The internalization of assembled Mg-ACP/PAA nanoparticles by MC3T3-E1 cells occurred through endocytosis,indicated by laser scanning confocal microscopy and cryo-soft X-ray tomography.Our results showed that cellular lipid membranes remained intact without pore formation after Mg-ACP/PAA particle penetration.The assembled Mg-ACP/PAA particles could be digested in cell lysosomes within 24 h under weak acidic conditions,thereby indicating the potential to efficiently deliver encapsulated functional molecules.Both the in vitro and in vivo results preliminarily demonstrated good biosafety of the inorganic-organic Mg-ACP/PAA hybrid nanoparticles,which may have potential for biomedical applications.

关键词： Inorganic-organic hybrid pH responsive ACP clusters Cellular degradation Cryo-soft X-ray tomography

Injectable melatonin-loaded carboxymethyl chitosan(CMCS)-based hydrogel accelerates wound healing by reducing inflammation and promoting angiogenesis and collagen deposition

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Journal of Materials Science & Technology 2021年第4期63卷 236-245页

作者： Kai Chen Changci Tong Jinge Yang Peifang Cong Ying liu Xiuyun Shi Xu liu Jun Zhang Rufei Zou Keshen Xiao Yuyang Ni Lei Xu Mingxiao Hou Hongxu Jin yunen liu Shangrao Normal University the Innovation Institute of Agricultural TechnologyCollege of Life ScienceShangrao 334001China Department of Emergency Medicine the General Hospital of Northern Theater CommandLaboratory of Rescue Center of Severe Trauma PLAShenyang l10016China Jiangxi Medical College Shangrao 334001China College of Physical Education Yanshan UniversityQinhuangdao 066004China Institute of Metal Research Chinese Academy of SciencesShenyang 110016China

Carboxymethyl chitosan(CMCS)-based hydrogels have antibacterial activity,and have shown the abilities of preventing wound infection,promoting cell proliferation,accelerating collagen deposition,and stimulating hyaluronic acid formation during wound healing.As a hormone produced by the pineal gland in humans and animals,melatonin promotes skin wound healing by regulating the release of inflammatory mediators and accelerating the proliferation and migration of cells,angiogenesis,and collagen deposition.However,the combined effects of CMCS and melatonin on wound healing remain unclear.Injectable CMCS-based hydrogels containing melatonin were prepared,and their healing effects were evaluated using a full-thickness cutaneous wound model in rats.Compared with the control and the hydrogel with no melatonin groups,the melatonin-loaded hydrogel significantly increased the percentage of wound closure,promoted the proliferation of granulation tissue and re-epithelialization,and accelerated collagen deposition.Additionally,the melatonin-loaded hydrogel promoted angiogenesis and vascular endothelial growth factor receptor protein expression and increased the expression of cyclooxygenase-2 and inducible nitric oxide synthase.The melatonin-loaded hydrogel also markedly increased the expression of collagen III,α-smooth muscle actin,and transforming growth factor-β1 proteins and reduced collagen I expression.These results suggest that the melatonin-loaded hydrogel promoted granulation tissue formation and accelerated wound healing by reducing inflammation and promoting angiogenesis and collagen deposition.

关键词： healing wound inflammation

Blueberry malvidin-3-galactoside modulated gut microbial dysbiosis and microbial TCA cycle KEGG pathway disrupted in a liver cancer model induced by HepG2 cells

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Food Science and Human Wellness 2020年第3期9卷 245-255页

作者： Zhen Cheng Jie Lin Ningxuan Gao Xiyun Sun Xianjun Meng Ruihai liu yunen liu Weisheng Wang Bin Li Yuehua Wang College of Food Science Shenyang Agricultural UniversityLiaoningChina National R&D Professional Center For Berry Processing Shenyang Agricultural UniversityLiaoningChina Key Laboratory of Healthy Food Nutrition and Innovative Manufacturing of Liaoning China Department of food Science Cornell UniversityIthacaNYUSA Emergency Medicine Department of General Hospital of Shenyang Military Command Laboratory of Rescue Center of Severe Trauma PLALiaoningChina Shenyang Blueberry Industry Co.LTD. LiaoningChina

HCC(Hepatocellular Carcinoma)is a critical health issue worldwide.Our previous animal experiment has confirmed that blueberry malvidin-3-galactoside(M3G)can regulate the progression of HCC.In this study,feces samples from the same batch of mice were collected to explore the regulatory mechanism of M3G on intestinal microbiota and microbial TCA cycle metabolism KEGG pathway in HCC mice based on 16S rRNA sequencing and metagenomics.Our results showed that blueberry M3G increased the microbial diversity and regulated the structure of intestinal microbiota in mice,such as increasing the abundance of Clostridia(butyric acid-producing bacteria),Oscillospira and Ruminococcus,and reducing the abundance of pathogenic Erysipelotrichi.Compared with the group of liver cancer and 5-fluorouracil,blueberry M3G significantly regulated microbial TCA cycle KEGG pathway via improving the expression of key proteins(porA,DLAT,aceE,PC and OGDH).Additionally,we found which the abundance of Muribaculum intestinale increased by blueberry M3G may be an important factor affecting the microbial TCA cycle KEGG pathway via the pearson correlation(R)analysis of protein and microbiota.Taken together,these results demonstrate that the blueberry M3G has the potential to be an intestinal microbiota regulator and an adjuvant to HCC therapy.

关键词： Blueberry malvidin-3-galactoside HCC metagenomics microbial TCA cycle KEGG pathway

静脉—动脉体外膜氧合辅助患者胃肠功能障碍的危险因素分析

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中国体外循环杂志 2024年第1期22卷 4-7,12页

作者：柏勇黄光庆赵旭史君星柳云恩沈阳医学院研究生院沈阳110034 湖北省十堰市人民医院重症医学科十堰442000 沈阳医学院树人国际学院沈阳110034

目的研究分析静脉-动脉体外膜氧合(V-A ECMO)辅助患者发生胃肠功能障碍的危险因素和对其预后的影响。方法回顾性分析2019年1月至2023年7月湖北省十堰市人民医院重症医学科成功撤机的V-A ECMO辅助患者52例,按照是否出现胃肠功能障碍分... 详细信息

目的研究分析静脉-动脉体外膜氧合(V-A ECMO)辅助患者发生胃肠功能障碍的危险因素和对其预后的影响。方法回顾性分析2019年1月至2023年7月湖北省十堰市人民医院重症医学科成功撤机的V-A ECMO辅助患者52例,按照是否出现胃肠功能障碍分为胃肠功能障碍组和非胃肠功能障碍组,其中胃肠功能障碍组29例,非胃肠功能障碍23例,通过组间单因素分析筛选出胃肠功能障碍的危险因素,经logistic回归分析确定影响胃肠功能障碍的危险因素。结果经过单因素分析表明较低V-A ECMO辅助流量、高血乳酸、较短时间主动脉球囊反搏(IABP)及ECMO辅助、较晚启动肠内营养、较大剂量去甲肾上腺素使用量为胃肠功能障碍的危险因素,通过多元logistic回归分析表明较短时间IABP辅助及相对较晚启动肠内营养为胃肠功能障碍的独立危险因素。结论 V-A ECMO辅助期间,较短时间IABP辅助及相对较晚启动肠内营养为其发生胃肠功能障碍的独立危险因素。

关键词：体外膜氧合胃肠功能障碍危险因素肠内营养

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眼科新进展 2021年第11期41卷 1021-1026页

作者：杨露露柳云恩陈颖欣锦州医科大学北部战区总医院研究生培养基地辽宁省锦州市121000 全军重症(战)创伤救治中心实验室辽宁省沈阳市110016 北部战区总医院眼科辽宁省沈阳市110016

目的探讨核因子E2相关因子2(Nrf2)/血红素加氧酶1(HO-1)信号通路介导的氧化应激反应对早期小鼠视网膜爆震伤的影响及其作用机制。方法取雄性C57BL/6小鼠60只随机分为对照组和模型组,对照组小鼠常规饲养,模型组小鼠接受爆震冲击处理。去... 详细信息

目的探讨核因子E2相关因子2(Nrf2)/血红素加氧酶1(HO-1)信号通路介导的氧化应激反应对早期小鼠视网膜爆震伤的影响及其作用机制。方法取雄性C57BL/6小鼠60只随机分为对照组和模型组,对照组小鼠常规饲养,模型组小鼠接受爆震冲击处理。去除建模过程中5只死亡小鼠,最终纳入对照组16只小鼠、6 h模型组19只小鼠、48 h模型组20只小鼠。分别于建模后6 h、48 h腹腔注射200 g·L^(-1)戊巴比妥钠过量麻醉处死小鼠,解剖取材。对各组小鼠视网膜组织进行HE染色,计数视网膜神经节细胞(RGC)并测量视网膜神经纤维层(RNFL)厚度。免疫组织化学染色检测各组小鼠视网膜组织Nrf2蛋白、HO-1蛋白、超氧化物歧化酶2(SOD2)蛋白表达情况。Western blot检测各组小鼠视网膜组织Nrf2蛋白、HO-1蛋白、SOD2蛋白、诱导型一氧化氮合酶(iNOS)蛋白、黑色素瘤分化相关基因5(MDA5)蛋白的相对表达量。结果与对照组相比,6 h模型组小鼠视网膜组织结构疏松,细胞排列紊乱,神经节细胞层、内核层及外核层出现核浓缩和空泡现象;RGC数减少(P<0.05),RNFL厚度增加(P<0.05);48 h模型组小鼠视网膜组织细胞排列更为杂乱疏松,RGC数明显减少(P<0.05),RNFL进一步增厚(P<0.05),并伴有新生血管生成。与对照组[(7.85±1.16)%]相比,6 h模型组小鼠视网膜组织Nrf2蛋白阳性细胞表达率升高至(16.78±1.38)%;48 h模型组进一步升高至(20.01±1.48)%,差异均有统计学意义(均为P<0.05)。与对照组[(4.67±0.98)%、(4.15±1.11)%]相比,6 h模型组小鼠视网膜组织HO-1蛋白、SOD2蛋白阳性细胞表达率分别升高至(7.95±1.27)%和(6.14±0.90)%;48 h模型组继续升高,分别为(12.34±1.48)%、(10.25±1.46)%,差异均有统计学意义(均为P<0.05)。与对照组相比,6 h模型组小鼠视网膜组织Nrf2蛋白、HO-1蛋白、SOD2蛋白、iNOS蛋白、MDA5蛋白相对表达量均升高,差异均有统计学意义(均为P<0.05);48 h模型组进一步升高,差异均有统计学意义(均为P<0.05)。结论Nrf2/HO-1信号通路介导的氧化应激反应参与早期视网膜爆震伤的发生,其作用机制与上调SOD2蛋白、MDA5蛋白、iNOS蛋白表达有关。

关键词：视网膜爆震伤核因子E2相关因子2 血红素加氧酶1 氧化应激反应

溃疡性结肠炎患者血清miR-15表达水平与炎性反应状态及预后的关系

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国际消化病杂志 2020年第1期40卷 41-46页

作者：刘丽柳云恩辽宁中医药大学附属第三医院内科辽宁沈阳110004 北部战区总医院急诊医学部辽宁沈阳110016

目的探讨溃疡性结肠炎(UC)患者血清miR-15的表达水平与炎性反应状态及预后的关系。方法选取2014年1月至2017年1月辽宁中医药大学附属第三医院及北部战区总医院收治的101例UC患者作为研究对象,其中UC缓解期45例,UC活动期56例,另选取同期5... 详细信息

目的探讨溃疡性结肠炎(UC)患者血清miR-15的表达水平与炎性反应状态及预后的关系。方法选取2014年1月至2017年1月辽宁中医药大学附属第三医院及北部战区总医院收治的101例UC患者作为研究对象,其中UC缓解期45例,UC活动期56例,另选取同期50例健康体检者作为对照组。通过RT-qPCR法检测所有受试者血清miR-15的相对表达量,比较不同程度UC患者血清miR-15的表达水平。分析血清miR-15表达水平与Mayo评分、Baron评分的相关性。采用多因素Logistic回归法分析影响UC患者复发的相关因素。结果UC活动期患者血清miR-15的相对表达量显著高于UC缓解期和对照组,差异均有统计学意义(P均<0.05)。UC活动期重度组患者血清miR-15的相对表达量、Mayo评分、Baron评分显著高于中度组和轻度组患者,差异均有统计学意义(P均<0.05)。相关性分析显示,miR-15的相对表达量与Mayo评分、Baron评分均呈正相关(P均<0.05)。多因素Logistic回归分析显示,性别、吸烟、pANCA、基底浆细胞增多、miR-15相对表达量与UC患者的复发密切相关。结论UC患者血清miR-15的相对表达量与炎性反应状态呈正相关,且与UC患者的复发关系密切。

关键词：溃疡性结肠炎 miR-15 炎性反应状态预后

PBL+课程思政在基础医学消化系统整合课中的应用与探索

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中国教育技术装备 2023年第12期 83-86,92页

作者：王旭光柳云恩张珉薄威王柏芳张忠沈阳医学院病理学教研室沈阳110034

通过调查问卷和期末结业成绩分析,对单独的理论授课、理论+PBL和PBL+课程思政等不同教学方式教学效果进行比较分析,结果显示PBL+课程思政这种教学模式能提高学生积极性与科研兴趣,加强基础与临床的结合,提升职业素养与激发爱国热情,从... 详细信息

通过调查问卷和期末结业成绩分析,对单独的理论授课、理论+PBL和PBL+课程思政等不同教学方式教学效果进行比较分析,结果显示PBL+课程思政这种教学模式能提高学生积极性与科研兴趣,加强基础与临床的结合,提升职业素养与激发爱国热情,从而提高学生的学业成绩,因此,认为“PBL+课程思政”是课程思政的有效方法,可以借鉴和推广。

关键词：课程思政消化系统整合课 PBL

蛋白质精氨酸甲基转移酶6调控前列腺癌发生的分子机制

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成都医学院学报 2015年第4期10卷 420-427页

作者：徐莹阎英柳云恩沈阳军区总医院放射治疗科沈阳110840 沈阳军区总医院急诊医学部全军重症战创伤救治中心实验室沈阳110840

目的探讨蛋白质精氨酸甲基转移酶6(PRMT6)调控前列腺癌发生的分子机制。方法通过免疫组织化学、Western blot、Real Time PCR、转染、克隆实验、流式细胞技术和Transwell实验研究PRMT6对前列腺癌细胞增殖、细胞周期及迁移的影响。结果... 详细信息

目的探讨蛋白质精氨酸甲基转移酶6(PRMT6)调控前列腺癌发生的分子机制。方法通过免疫组织化学、Western blot、Real Time PCR、转染、克隆实验、流式细胞技术和Transwell实验研究PRMT6对前列腺癌细胞增殖、细胞周期及迁移的影响。结果研究发现,PRMT6在前列腺癌组织及前列腺癌细胞系中呈高表达状态,PRMT6表达改变与促癌基因PSA和KLK2成正相关,证实PRMT6通过调控AR下游靶基因促进前列腺癌发生。此外,PRMT6促进前列腺癌细胞22Rv1和LNCaP的细胞周期进程,促进细胞增殖及迁移。结论 PRMT6通过调控AR下游靶基因促进前列腺癌细胞的增殖及迁移,从而促进前列腺癌的发生发展。

关键词：前列腺癌蛋白质精氨酸甲基转移酶6 凋亡分子机制

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新型小鼠脑爆震伤模型的建立及研究

中华急诊医学杂志 2019年第1期28卷 44-49页

作者：佟昌慈柳云恩张玉彪丛培芳施琳史秀云刘颖侯明晓金红旭北部战区总医院急诊医学部全军重症(战)创伤救治中心实验室及辽宁省重症创伤和器官保护重点实验室沈阳110116

目的研发一种新型爆震伤模拟装置建立小鼠脑爆震伤模型,并研究小鼠脑爆震伤的损伤机制。方法30只昆明小鼠随机(随机数字法)分为正常对照组(Ctrl组)和脑爆震伤模型组(TBI组)。利用自主研发的爆震伤模拟装置制备脑爆震伤小鼠模型,并采用Mo... 详细信息

目的研发一种新型爆震伤模拟装置建立小鼠脑爆震伤模型,并研究小鼠脑爆震伤的损伤机制。方法30只昆明小鼠随机(随机数字法)分为正常对照组(Ctrl组)和脑爆震伤模型组(TBI组)。利用自主研发的爆震伤模拟装置制备脑爆震伤小鼠模型,并采用Morris水迷宫、伊文思蓝(EB)实验和HE染色,观察小鼠脑部经冲击波暴露后空间记忆能力、血脑屏障、脑组织病理改变的影响。Western-blot方法检测脑损伤标志物Tau、S100β、胆碱,炎症相关因子IL-1β、IL-4、IL-6、IL-10、NF-κB,凋亡相关因子Bcl-2、Bax、Caspase3和氧化应激相关因子IREα、MDA5、COX2、SOD1和SOD2的蛋白表达。两组间计量资料比较采用成组t检验。结果与Ctrl组(11.2±2.1)s相比,TBI组小鼠寻找平台时间为(54.6±8.4)s,明显增加(t=-19.330,P<0.05);TBI组小鼠EB渗出量比Ctrl组明显增高3.22倍(t=-13.903,P<0.05);病理染色可见海马区神经元损伤,同时TBI诱导脑组织损伤标志物Tau(0.26±0.03vs0.46±0.04,t=-9.788,P<0.05)、S100β(0.54±0.03vs.0.74±0.02,t=-12.433,P<0.05)和胆碱(0.54±0.05vs0.80±0.04,t=-7.970,P<0.05),炎性因子IL-1β(0.22±0.04vs0.31±0.05,t=-3.431,P<0.05)、IL-4(0.65±0.02vs0.97±0.03,t=-18.927,P<0.05)、IL-6(0.88±0.05vs1.07±0.08,t=-9.488,P<0.05)和NF-κB(0.80±0.06vs1.03±0.07,t=-4.507,P<0.05),促凋亡因子Caspase-3(0.44±0.03vs0.60±0.05,t=-4.472,P<0.05)和Bax(0.66±0.04vs0.78±0.04,t=-13.007,P<0.05),促氧化因子IREα(0.72±0.06vs1.07±0.04,t=-9.665,P<0.05)、MDA5(0.47±0.02vs0.77±0.02,t=-23.678,P<0.05)和COX2(0.70±0.07vs0.86±0.02,t=-6.421,P<0.05)的蛋白表达,降低抑炎因子IL-10(1.14±0.06vs0.74±0.07,t=13.729,P<0.05)、抑凋亡因子Bcl-2(0.72±0.05vs0.46±0.02,t=11.491,P<0.05)及抑氧化应激因子SOD1(1.17±0.05vs0.99±0.01,t=7.731,P<0.05)和SOD2(0.81±0.05vs0.61±0.04,t=10.257,P<0.05)的蛋白表达。结论脑爆震伤可损伤小鼠空间学习记忆能力、破坏血脑屏障、损伤海马区神经元,同时促进脑损伤标志物的表达,诱导炎症反应、氧化应激反应及细胞凋亡的发生,成功通过自主研发的爆震伤模拟装置建立小鼠脑爆震伤模型。

关键词：脑爆震伤模拟装置空间记忆学习能力血脑屏障损伤